Heterotrimeric G-protein alpha-12 (Gα12) subunit promotes oral cancer metastasis

Oral squamous cell carcinoma (OSCC) has a propensity to spread to the cervical lymph nodes (LN). The presence of cervical LN metastases severely impacts patient survival, whereby the two-year survival for oral cancer patients with involved LN is ~30% compared to over 80% in patients with non-involved LN. Elucidation of key molecular mechanisms underlying OSCC metastasis may afford an opportunity to target specific genes, to prevent the spread of OSCC and to improve patient survival. In this study, we demonstrated that expression of the heterotrimeric G-protein alpha-12 (Gα12) is highly up-regulated in primary tumors and LN of OSCC patients, as assessed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). We also found that exogenous expression of the constitutively activated-form of Gα12 promoted cell migration and invasion in OSCC cell lines. Correspondingly, inhibition of Gα12 expression by shRNA consistently inhibited OSCC cell migration and invasion in vitro. Further, the inhibition of G12 signaling by regulator of G-protein signaling (RGS) inhibited Gα12-mediated RhoA activation, which in turn resulted in reduced LN metastases in a tongue-orthotopic xenograft mouse model of oral cancer. This study provides a rationale for future development and evaluation of drug candidates targeting Gα12-related pathways for metastasis prevention.     

Prevalence of glycemic variability and factors associated with the glycemic arrays among end-stage kidney disease patients on chronic hemodialysis

Glycemic variability (GV) confers a significantly higher risk of diabetic-related complications, especially cardiovascular. Despite extensive research in this area, data on end-stage kidney disease (ESKD) patients on chronic hemodialysis are scarce. This study aims to determine the magnitude of GV among ESKD (diabetic vs nondiabetic) patients and its associated factors on hemodialysis days (HDD) and non-hemodialysis days (NHDD) where postulation of a higher GV observed among diabetic on HDD.We recruited 150 patients on hemodialysis, 93 patients with type 2 diabetic (DM-ESKD), and 57 with nondiabetic (NDM-ESKD). The GV indices (standard deviation [SD] and percentage coefficient variant [%CV]) were obtained from 11-point and 7-point self-monitoring blood glucose (fasting to post-meal) (SMBG) profiles on HDD and NHDD. The GV indices and its associated factors of both DM-ESKD and NDM-ESKD were analyzed to compare HDD vs NHDD.Mean blood glucose on HDD was 9.33 [SD 2.7, %CV 30.6%] mmol/L in DM-ESKD compared with 6.07 [SD 0.85, %CV 21.3%] mmol/L in NDM-ESKD (P = <.01). The DM-ESKD group experienced significantly above target GV indices compared to NDM-ESKD on both HDD and NHDD, particularly in the subgroup with HbA1c 8–10% (P = <.01). Presence of diabetes, older age, hyperlipidemia, HbA1c, ferritin levels, and albumin were identified as factors associated with GV.DM-ESKD patients have above-target GV indices, especially on HDD, therefore increasing their risk of developing future complications. We identified high HbA1c, older age group, presence of hyperlipidemia, ferritin levels, and albumin as factors associated with GV indices that may be used as surrogate markers for GV. Since these groups of patients are vulnerable to CVD mortality, urgent attention is needed to rectify it.     

A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury

Acute kidney injury (AKI) following Eastern Russell’s viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity caused by these toxins is still unclear. In the present study, we purified two proteins from D. siamensis venom, namely RvPLA₂ and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA₂ to be snake venom phospholipase A₂ (SVPLA₂) from Thai D. siamensis venom, whereas RvMP exhibited the presence of a factor X activator with two subunits. In vitro and in vivo pharmacological studies demonstrated myotoxicity and histopathological changes of kidney, heart, and spleen. RvPLA₂ (3–10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA₂ or RvMP (300 µg/kg, i.p.) for 24 h, diffuse glomerular congestion and tubular injury with minor loss of brush border were detected in envenomed mice. RvPLA₂ and RvMP (300 µg/kg; i.p.) also induced congestion and tissue inflammation of heart muscle as well as diffuse congestion of mouse spleen. This study showed the significant roles of PLA₂ and SVMP in snake bite envenoming caused by Thai D. siamensis and their similarities with observed clinical manifestations in envenomed victims. This study also indicated that there is a need to reevaluate the current treatment strategies for Thai D. siamensis envenoming, given the potential for irreversible nephrotoxicity.     

Acaricidal activity of Cymbopogon citratus and Azadirachta indica against house dust mites

Objective

To examine the acaricidal effects of the essential oil of Cymbopogon citratus leaf extract (lemongrass) and ethanolic Azadirachta indica leaf extract (neem) against house dust mites Dermatophagoides farinae (D. farinae) and Dermatophagoides pteronyssinus (D. pteronyssinus).

Methods

Twenty-five adults mites were placed onto treated filter paper that is soaked with plant extract and been tested at different concentrations (50.00%, 25.00%, 12.50%, 6.25% and 3.13%) and exposure times (24hrs, 48hrs, 72hrs and 96 hrs). All treatments were replicated 7 times, and the experiment repeated once. The topical and contact activities of the two herbs were investigated.

Results

Mortalities from lemongrass extract were higher than neem for both topical and contact activities. At 50 % concentration, both 24 hrs topical and contact exposures to lemongrass resulted in more than 91% mortalities for both species of mites. At the same concentration and exposure time, neem resulted in topical mortalities of 40.3% and 15.7% against D. pteronyssinus and D. farinae respectively; contact mortalities were 8.0% and 8.9% against the 2 mites, respectively. There was no difference in topical mortalities of D. pteronyssinus from exposure to concentrations of lemongrass and neem up to 12.50%; lemongrass was more effective than neem at the higher concentrations.

Conclusions

Generally, topical mortalities of D. farinae due to lemongrass are higher than that due to neem. Contact mortalities of lemongrass are always higher that neem against both species of mites.     

天津地区胃癌危险因素病例-对照研究

目的从天津地区胃癌发病的危险因素方面探讨胃癌的发病机制,旨在为胃癌的病因学研究和防治工作提供线索和依据。方法对天津地区100例胃镜检查或手术后,经病理检查确诊为胃癌患者为病例组,并以同期胃镜诊断为慢性浅表性胃炎和慢性萎缩性胃炎患者109例作为对照组,均通过统一制表进行相关因素的问卷调查,专人登记。对调查结果进行了Logistic回归分析,以确定饮食、情绪、生活习惯等危险因素与胃癌发生的关系。结果嗜酒和有恶性肿瘤家族史均会很大程度上增加患胃癌的危险性,嗜酒（酒精量〉40g／d）患胃癌的OR值是2．448（95％CI：1．157～5．182）,直系亲属患恶性肿瘤发生胃癌的OR值是3．469（95％CI：1．392～8．644）。结论嗜酒和有恶性肿瘤家族史均会很大程度上增加患胃癌的危险程度。     

LC–DAD–ESI-MS analysis of nitric oxide inhibitory fractions of tenggek burung (Melicope ptelefolia Champ. ex Benth.)

Solvent–solvent fractionation of the methanolic extract of the popular Malay traditional vegetable “tenggek burung” (Melicope ptelefolia), followed by nitric oxide inhibition assay on RAW 264.7 cells revealed that the most active components reside mainly in hexane and dichloromethane fractions. Online profiling of the nitric oxide (NO) inhibitive fractions of the tenggek burung using liquid chromatography coupled diode array detection and electrospray ion-trap tandem mass spectroscopy (LC–DAD–ESI-MSⁿ), has identified seven constituents. The compounds were identified as kokusaginine (1), compound 2, [kokusagine, (2a) or 5-methoxymaculine (2b)], 2,4,6-trihydroxy-3-prenylacetophenone (3), 2,4,6-trihydroxy-3-geranylacetophenone (4), 2,4,6-trihydroxy-3-geranylgeranylacetophenone (5), 3-[4-O-(3,7-dimethyl-2,6-octadienyl)phenyl]-2-propenoic acid (6) and 2,4,6-trihydroxy-3-farnesylgeranylacetophenone (7). The identity of compounds 1, 4 and 6 were unequivocally confirmed by isolation and spectroscopic evidences, other constituents are tentatively identified, based on their UV, MS, MSⁿ and comparison with literature data. Kokusaginine (1) demonstrated in vitro activity on NO inhibition in murine peritoneal macrophages.     

西藏那曲冬虫夏草无形型的研究

目的 :分离鉴定西藏那曲冬虫夏草无性型真菌。方法 :采用子囊孢子、织、僵虫、体液分离的方法从巴青、索县、比如 3县分离冬虫夏草无性型菌株。结果 :采用 4种方法获得了性状特证与中国被毛孢相同的无性型菌株。结论 :中国被毛孢是西藏那曲冬虫夏草的无性型。     

H-Gly-Hisψ(NHCO)Lys-OH,partially modified retro-inverso analogue of the growth factor glycyl-L-histidyl-L-lysine with enhanced enzymatic stability

A partially retro-inverso analogue of the natural growth factor GHK was synthesized, in which the —CONH— bond between histidine and lysine was modified as —NHCO—. This modification is not expected to perturb the spatial distribution of the side-chains, and therefore the binding processes, compared to the native peptide. In the synthesis of the analogue two possible systems for deblocking of N^π-Born group of histidine have been applied and compared. An alternative method is also described for the incorporation of malonyllysine into the peptide chain. When evaluated with respect to resistance toward degradation by human plasma in vitro, the new peptide analogue showed approximately a ten-fold increase in stability versus the parent peptide.     

DELAYED TRAUMATIC EXTRADURAL HAEMATOMAS

A total of 76 patients with traumatic extradural haematoma were treated within a period of 3 years. Four patients developed delayed extradural haematomas. These cases are reported in view of the unusual sequence and the importance of early diagnosis.